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The complement system plays a crucial role in regulating the inflammatory responses in kidney transplantation, potentially contributing to early decline in kidney function. Ischemia–reperfusion injury (IRI) is among the factors affecting graft outcomes and a primary contributor to delayed graft function. Complement activation, particularly the alternative pathway, participates in the pathogenesis of IRI, involving all kidney compartments. In particular, tubular epithelial cells often acquire a dysfunctional phenotype that can exacerbate complement activation and kidney damage. Currently, complement-modulating drugs are under investigation for the treatment of kidney diseases. Many of these drugs have shown potential therapeutic benefits, but no effective clinical treatments for renal IRI have been identified yet. In this review, we will explore drugs that target complement factors, complement receptors, and regulatory proteins, aiming to highlight their potential value in improving the management of renal IRI. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of renal significance (MGRS) refers to a group of renal disorders caused by a monoclonal immunoglobulin (MIg), secreted by a non-malignant B-cell clone. Unlike overt multiple myeloma or B-cell proliferation, MGRS does not meet those diagnostic criteria. However, it is associated with significant morbidity, due to severe renal, and sometimes systemic, lesions induced by the MIg. Early recognition is crucial, as chemotherapy to suppress MIg secretion often improves outcomes. The spectrum of renal diseases in MGRS is broad, including both well-known conditions like AL amyloidosis and newly described lesions. Kidney biopsy is essential to determine the specific lesion associated with MGRS and assess its severity. Diagnosis involves integrating morphologic alterations using techniques such as light microscopy, immunofluorescence (IF), electron microscopy, and, in some cases, IF staining for Ig isotypes, immunoelectron microscopy, and proteomic analysis. Additionally, a complete hematologic evaluation, including serum and urine protein electrophoresis, immunofixation, and a serum-free light-chain assay, is necessary. [ABSTRACT FROM AUTHOR]

Background: Anderson–Fabry disease (AFD) is a rare genetic disorder characterized by a deficiency of α-galactosidase A activity and the accumulation of glycosphingolipids in tissues, which leads to multiorgan damage. Cardiovascular magnetic resonance (CMR) and the T1 mapping technique are essential tools for the assessment of AFD cardiac involvement. Moreover, the T1 mapping technique has proved to be a successful non-invasive method for the early detection of patients most at risk for kidney disease. We evaluated the application of MRI in patients with AFD to assess renal involvement. Methods: We conducted a retrospective analysis of 19 patients (Group A) with histologically proven AFD who underwent routine CMR examinations for the evaluation of cardiac involvement, selecting specific sequences that also showed the left kidney, compared to a control population (Group B, 19 patients) without kidney disease. A Spearman's rank-order correlation was run to assess the relationship between the T1 mapping values of the heart and kidney in Group A and between the kidneys of Groups A and B. Results: There was a positive correlation between the heart and kidney T1 values in Group A (rho = 0.32). More interestingly, we observed a negative correlation between the kidney values of both groups (Group A mean 1284 ± 137 ms, Group B mean 1073 ± 57 ms, rho = −0.38), which is probably related to the presence of microvascular damage and infiltrates in the kidneys of AFD patients. Conclusions: To our knowledge, these results are the first to highlight the key value of T1 mapping in assessing pathological changes and aiding in the non-invasive diagnosis of renal involvement in AFD. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was isolated in January 2020 and, on March, the WHO declared the status of a pandemic. It causes a cytokine release syndrome, called “cytokine storm,” characterized by systemic inflammation involving elevated levels of cytokines and hyperactivation of immune cell; this profound alteration in the immune system led to an overshooting inflammatory response contributing to morbidity and mortality. Solid organ transplant recipients are at particularly higher risk of developing critical coronavirus disease 2019 (COVID-19) due to chronic immunosuppression; in fact, establishing the balance between infection and rejection in any transplant recipient is the principal aim when prescribing immunosuppression. Tocilizumab, a humanized monoclonal antibody against interleukin-6 (IL-6) receptor widely adopted in adult rheumatoid arthritis, is used as rescue therapy for chronic antibody-mediated rejection in kidney transplantation. Data about the use of tocilizumab for treating acute kidney graft dysfunction in a setting of kidney-transplanted patients affected by COVID-19 are lacking. In this case study, we discuss the case of kidney transplant recipient with proven SARS-CoV-2 infection that develops acute graft dysfunction and the management of immunosuppression with concomitant tocilizumab administration.

The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells. Among them, mTOR and SGLT-2 inhibitors have garnered attention due to their diverse effects: mTOR inhibitors regulate cellular growth, metabolism, and immune responses, while SGLT-2 inhibitors regulate glucose reabsorption in the kidneys, resulting in various beneficial metabolic effects. Importantly, these drugs may act synergistically by influencing senescence processes and pathways. Although direct studies on the combined effects of mTOR inhibition and SGLT-2 inhibition on age-related processes are limited, this review aims to highlight the potential synergistic benefits of these drugs in targeting senescence. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are a heterogeneous group of antigen-presenting cells crucial for fostering allograft tolerance while simultaneously supporting host defense against infections and cancer. Within the tumor microenvironment, DCs can either mount an immune response against cancer cells or foster immunotolerance, presenting a dual role. In immunocompromised individuals, posttransplant malignancies pose a significant health concern, with DCs serving as vital players in immune responses against cancer cells. Both recipient- and donor-derived DCs play a critical role in the rejection process, infiltrating the transplanted organ and sustaining T-cell responses. The use of immunosuppressive drugs represents the predominant approach to control this immunological barrier in transplanted organs. Evidence has shed light on the immunopharmacology of these drugs and novel strategies for manipulating DCs to promote allograft survival. Therefore, comprehending the mechanisms underlying this intricate microenvironment and the effects of immunosuppressive therapy on DCs is crucial for developing targeted therapies to reduce graft failure rates. This review will delve into the fundamental immunobiology of DCs and provide a detailed exploration of their clinical significance concerning alloimmune responses and posttransplant malignancies. [ABSTRACT FROM AUTHOR]

Background The known risks and benefits of native kidney biopsies are mainly based on the findings of retrospective studies. The aim of this multicentre prospective study was to evaluate the safety of percutaneous renal biopsies and quantify biopsy-related complication rates in Italy. Methods The study examined the results of native kidney biopsies performed in 54 Italian nephrology centres between 2012 and 2020. The primary outcome was the rate of major complications 1 day after the procedure, or for longer if it was necessary to evaluate the evolution of a complication. Centre and patient risk predictors were analysed using multivariate logistic regression. Results Analysis of 5304 biopsies of patients with a median age of 53.2 years revealed 400 major complication events in 273 patients (5.1%): the most frequent was a ≥2 g/dL decrease in haemoglobin levels (2.2%), followed by macrohaematuria (1.2%), blood transfusion (1.1%), gross haematoma (0.9%), artero-venous fistula (0.7%), invasive intervention (0.5%), pain (0.5%), symptomatic hypotension (0.3%), a rapid increase in serum creatinine levels (0.1%) and death (0.02%). The risk factors for major complications were higher plasma creatinine levels [odds ratio (OR) 1.12 for each mg/dL increase, 95% confidence interval (95% CI) 1.08–1.17], liver disease (OR 2.27, 95% CI 1.21–4.25) and a higher number of needle passes (OR for each pass 1.22, 95% CI 1.07–1.39), whereas higher proteinuria levels (OR for each g/day increase 0.95, 95% CI 0.92–0.99) were protective. Conclusions This is the first multicentre prospective study showing that percutaneous native kidney biopsies are associated with a 5% risk of a major post-biopsy complication. Predictors of increased risk include higher plasma creatinine levels, liver disease and a higher number of needle passes. [ABSTRACT FROM AUTHOR]

The cellular and clinical effect of sirolimus on Kaposi's sarcoma in renal-transplant recipients is investigated. Results reveal that sirolimus inhibits the progression of dermal Kaposi's sarcoma in kidney-transplant recipients while providing effective immunosuppression.